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Colon cancer shuts down receptor that could shut it down
Date:4/13/2009

with much less potency. That got Dr. Ganapathy thinking about a place where butyrate levels were already high the colon which led to his discovery that the receptor was also on colon cells.

Butyrate plays other protective roles in colon cancer. In 2004, MCG researchers identified a gene, SLC5A8, that transports butyrate inside cells where it inhibits the enzyme HDAC, which gets upregulated in cancer to produce the uncontrolled cell growth that is a disease hallmark.

"If you block HDAC, you can kill the cancer cell," Dr. Ganapathy says.

Several synthetic HDAC inhibitors are under study for a variety of cancers at institutions such as the MCG Cancer Center. Unfortunately, just like the newly found GPR109A receptor, cancer also silences the SLC5A8 butyrate transporter. In his current study, the researcher found the receptor was silenced in 15 of 18 colon cancer patients.

"Colon cancer does not want butyrate produced by bacteria to come inside so it silences the transporter. It also does no want butyrate to act on the cell from the outside so it silences the receptor," Dr. Ganapathy says. "It does not want to have anything to do with butyrate."

Because the compounds that reactivate the receptor also reactivate the transporter, finding a way to mitigate cancer's attempts to silence the genes would create a two-prong attack against the cancer.

Mega doses of butyrate reportedly taste bad. But Dr. Ganapathy believes taking large amounts of niacin, something many patients already do for high cholesterol, is a good substitute. In fact, he wants to move ahead with clinical trials that compare the course of colon cancer patients who eat a high fiber diet or receive butyrate or niacin therapy along with taking DNA methylation inhibitors that keep GPR109A open for business.

He also wants to determine if his theory that inflammation also suppresses the receptor holds true. "We think receptor activation by butyrate s
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert  

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